DNA Damage Induced By UVA And UVB In Squamous Cell Carcinoma Progression
Funder
National Health and Medical Research Council
Funding Amount
$65,000.00
Summary
Australia has the highest incidence of skin cancer in the world. This results from immigration of individuals with fair skin to Australia. Skin cancer is three times as common as all other cancers combined. Overall, the incidence of skin cancer continues to rise in Australia and it will be several years before the true effectiveness of preventative programs are known. In the meantime, 1000 Australians die each year from skin cancer. Modern sunscreens, even those with high SPF and labelled as bro ....Australia has the highest incidence of skin cancer in the world. This results from immigration of individuals with fair skin to Australia. Skin cancer is three times as common as all other cancers combined. Overall, the incidence of skin cancer continues to rise in Australia and it will be several years before the true effectiveness of preventative programs are known. In the meantime, 1000 Australians die each year from skin cancer. Modern sunscreens, even those with high SPF and labelled as broad spectrum do not protect very well from UVA, though they are very effective UVB filters. Most sunscreens absorb or reflect only about 50% as much UVA as UVB. Thus sunscreen use alters the spectrum of UV received. This is an important issue, because if sunscreens are used to prolong sun exposure they will selectively increase the amount of UVA reaching the skin, and the sun contains a lot more UVA than UVB. There is only limited evidence to suggest they protect from skin cancer in humans whereas there is good evidence that they protect from precursor lesions. We have developed a new hypothesis, that UVB is primarily responsible for development of preneoplastic lesions (solar keratosis and dysplastic nevi) whereas UVA plays a relatively more important role in their progression to malignancy. This hypothesis would explain why sunscreens are more effective at preventing nevi and solar keratosis formation than they are at preventing melanoma and squamous cell carcinoma. Until the action spectrum defining the wavelengths responsible for skin cancer induction is known, the optimal methods for protection from skin cancer will be difficult if not impossible to design. That different wavelengths may be involved in different phases of skin cancer development in humans is a novel hypothesis: if it is correct it will have profound implications for both the design of sunscreens and our current public health programmes for skin cancer prevention.Read moreRead less
Cellular And Molecular Determinants Of Preleukaemic And Leukaemic Stem Cells
Funder
National Health and Medical Research Council
Funding Amount
$292,635.00
Summary
It has recently become evident that the formation, growth and relapse of many cancers is driven by a rare population of cancer stem cells (CSCs) that have the unique ability to propagate new tumours and are highly resistant to current therapies. However, which normal cells are transformed into CSCs is not known. We will take a potent cancer gene found in leukaemia, and switch it on and off in specific blood cells in mice to determine which healthy cells can be turned into leukaemic stem cells.
Interactions Between Hedgehog And Ras Signaling In Lung Adenocarcinoma
Funder
National Health and Medical Research Council
Funding Amount
$295,983.00
Summary
Lung cancer is a common and lethal disease in our community. In this project, we explore how signaling pathways that regulate the development of the lung in embryos contribute to the initation and progression of lung cancer. To do this, we use a mouse model of lung cancer in which we can activate embryonic signaling pathways in adult mice to study there effect on the disease. Understanding these pathways will help us to better treat and prevent lung cancer in humans.
Therapeutic Strategies In Epithelial Cancer Through Signalling Inhibition Of The Epidermal Growth Factor Receptor.
Funder
National Health and Medical Research Council
Funding Amount
$136,250.00
Summary
The growth of cancer cells is regulated by many factors, including the presence of growth receptors on the surface of cancer cells. The epidermal growth factor receptor (EGFR) is present in some normal tissues, but is highly expressed on many common cancers, including brain, breast, lung, head and neck, colon and prostate cancer. We are developing a number of potential therapeutic compounds that act by inhibiting the EGFR in cancer cells. These compounds include a novel monoclonal antibody that ....The growth of cancer cells is regulated by many factors, including the presence of growth receptors on the surface of cancer cells. The epidermal growth factor receptor (EGFR) is present in some normal tissues, but is highly expressed on many common cancers, including brain, breast, lung, head and neck, colon and prostate cancer. We are developing a number of potential therapeutic compounds that act by inhibiting the EGFR in cancer cells. These compounds include a novel monoclonal antibody that binds to EGFR and inhibits its function, and a small molecule that binds to a portion of the EGFR inside cancer cells and also inhibits function. Both of these compounds prevent tumour growth in laboratory studies. This project will examine the mechanisms of action of these compounds, and explore ways to improve their anti-cancer effect. We have also shown that combining these compounds with other therapeutics eg chemotherapy markedly enhances their anti-cancer effect. We will further examine the mechanisms of these effects, and also determine if radiotherapy has additive anti-cancer effects. These studies will provide a basis for improved therapies for cancers overexpressing the EGFR.Read moreRead less
Development Of Anti-metastatic And Tumour Targeting Reagents By Design Of Inhibitors To Specific Eph/ephrin Cell-cell
Funder
National Health and Medical Research Council
Funding Amount
$200,000.00
Summary
Metastatic disease, malignant melanoma in particular, is a health issue of considerable global importance with 1,000 fatal melanoma cases- year in Australia alone. While progress has been made on prevention and early diagnosis, no curative treatment exists for stage IV melanoma. Tumour progression and the acquisition of metastatic competence primarily reflect dysregulation of cell adhesion and cell motility rather than proliferation and survival. In this context, Eph receptor tyrosine kinases (E ....Metastatic disease, malignant melanoma in particular, is a health issue of considerable global importance with 1,000 fatal melanoma cases- year in Australia alone. While progress has been made on prevention and early diagnosis, no curative treatment exists for stage IV melanoma. Tumour progression and the acquisition of metastatic competence primarily reflect dysregulation of cell adhesion and cell motility rather than proliferation and survival. In this context, Eph receptor tyrosine kinases (Ephs) and their membrane-bound ephrin ligands are crucial mediators of cell adhesion and motility and are notably overexpressed in metastatic tumours rather than primary (benign) lesions5. Our laboratories were the first to identify EphA3 7, and one of the first to isolate its ligand, ephrin-A5. EphA3 was isolated from acute lymphoblastoid leukemia and malignant melanoma patients, where increasing expression levels correlate with metastatic progression. Soluble, non-clustered forms of Ephs and ephrins are effective inhibitors of Eph activity 3 and provide opportunities to generate specific drugs for cancer therapy. We now propose a research and development program for the development of EphA3-specific drugs and their production for pre-clinical and clinical evaluation for placement onto a national and international market.Read moreRead less
Analysis Of The Apoptotic And Therapeutic Effects Of Histone Deacetylase Inhibitors On Multiple Myeloma
Funder
National Health and Medical Research Council
Funding Amount
$287,321.00
Summary
Multiple myeloma (MM) is an incurable progressive cancer of plasma cells within blood. It is the second most common blood cancer and represents 2% of all cancer-related deaths. Statistics show increasing incidence and decreasing age of onset. The cause and progression of MM is poorly understood and current treatments are frequently followed by relapse. This project will assess exciting new therapies against the survival of MM cells leading to more effective treatments in the future.
Identifying The Targets Of MiRNA Regulation In Cancer
Funder
National Health and Medical Research Council
Funding Amount
$290,600.00
Summary
microRNAs are noncoding RNAs with fundamental functions in biology and significant roles disease. microRNAs control gene expression by destroying RNA or controlling its translation into cellular proteins. To determine how certain microRNAs cause human disease it is essential to know their RNA targets. We are developing methods to identify these targets and aim to apply these methods to identify the targets of microRNAs with known roles in cancer.
Identification And Functional Evaluation Of MicroRNAs And Their Target Genes That Regulate Breast Cancer Metastasis
Funder
National Health and Medical Research Council
Funding Amount
$607,773.00
Summary
Breast cancer is the major cause of cancer-associated death in Australian women. Once the disease has spread to other organs, as occurs in about 20% of cases, our ability to treat the disease is limited and mortality is high, leading to an enormous social and economic cost New therapies for advanced disease are needed urgently. To facilitate this, we need to understand the molecular regulation of metastasis to distant organs and use this knowledge to develop new molecular targeted therapies.
Understanding The Development Of Pancreatic Islet Cell Tumours
Funder
National Health and Medical Research Council
Funding Amount
$579,163.00
Summary
We will use mouse models of pancreatic cancer that we have established previously to investigate the molecular basis of the development and progression of tumours in the insulin-producing cells of the pancreas. We propose to manipulate a small number of candidate genes using established islet cultures and new mouse models in order to characterise the effect they have on islet cell biology and tumorigenesis.
BIOLOGICAL STUDIES OF A NEW RECURRENT FUSION GENE FOUND IN T-CELL LEUKAEMIA
Funder
National Health and Medical Research Council
Funding Amount
$187,925.00
Summary
Chromosome translocation, in which breaks occur in two chromosomes and rejoin to form two new hybrid chromosomes, is a common genetic alteration in leukaemia. Translocations have been invaluable in identifying genes important in the development of leukaemia. The genetic consequence of translocation is either the deregulation of critical genes adjacent to the breakpoints or the formation of new hybrid genes with novel properties. We have identified the genes at the breakpoints of a T-cell leukaem ....Chromosome translocation, in which breaks occur in two chromosomes and rejoin to form two new hybrid chromosomes, is a common genetic alteration in leukaemia. Translocations have been invaluable in identifying genes important in the development of leukaemia. The genetic consequence of translocation is either the deregulation of critical genes adjacent to the breakpoints or the formation of new hybrid genes with novel properties. We have identified the genes at the breakpoints of a T-cell leukaemia translocation involving chromosomes 4 and 11. The chromosome 11 gene, NUP98, is known to be involved in two other translocations in acute myeloid leukaemia but not in T-cell leukaemia. The chromosome 4 gene RAP1GDS has not been previously shown to be involved in human cancer. This project seeks to understand how the fusion protein NUP98-RAP1GDS (NRG) plays a role in the origin of leukaemia.Read moreRead less